ArticleInternational journal of molecular sciences2022
The PSI Domain of the MET Oncogene Encodes a Functional Disulfide Isomerase Essential for the Maturation of the Receptor Precursor.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting Adaptive and Innate Immune Responses with Covalent Aptamers.Journal of the American Chemical Society · 2026Article
- Plexin A2 regulated the metastasis in breast cancer through MCM7.BMC cancer · 2026Article
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
- Review
- Bioactive Products Targeting C-Met As Potential Antitumour Drugs.Anti-cancer agents in medicinal chemistry · 2025Review
- Single-molecule imaging and molecular dynamics simulations reveal early activation of the MET receptor in cells.Nature communications · 2024Article
- Protein disulfide isomerase plays a crucial role in mediating chemically-induced, glutathione depletion-associated hepatocyte injury in vitro and in vivo.Cell communication and signaling : CCS · 2024Article
- The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Subtelomeric plasticity contributes to gene family expansion in the human parasitic flatworm Schistosoma mansoni.BMC genomics · 2024Article
- An Observatory for theCancers · 2023Review
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
The tyrosine kinase receptor encoded by the MET oncogene has been extensively studied. Surprisingly, one extracellular domain, PSI, evolutionary conserved between plexins, semaphorins, and integrins, has no established function. The MET PSI sequence contains two CXXC motifs, usually found in protein disulfide isomerases (PDI). Using a scrambled oxidized RNAse enzymatic activity assay in vitro, we show, for the first time, that the MET extracellular domain displays disulfide isomerase activity, abolished by PSI domain antibodies. PSI domain deletion or mutations of CXXC sites to AXXA or SXXS result in a significant impairment of the cleavage of the MET 175 kDa precursor protein, abolishing the maturation of α and β chains, of, respectively, 50 kDa and 145 kDa, disulfide-linked. The uncleaved precursor is stuck in the Golgi apparatus and, interestingly, is constitutively phosphorylated. However, no signal transduction is observed as measured by AKT and MAPK phosphorylation. Consequently, biological responses to the MET ligand-hepatocyte growth factor (HGF)-such as growth and epithelial to mesenchymal transition, are hampered. These data show that the MET PSI domain is functional and is required for the maturation, surface expression, and biological functions of the MET oncogenic protein.
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